The traditional way of doing a donor transplant is to give high doses of chemotherapy and radiation before giving the stem cells. However, high doses of chemotherapy and radiation can have serious side-effects. The doctors think that the transplant will be safer and more likely to be successful with reduced doses of chemotherapy and radiation. The purpose of this study is to find out how good a combination of chemotherapy and radiation at reduced doses followed by a cord blood transplant are at treating cancer.

The stem cells chosen for the transplant are from umbilical cord blood. Umbilical cord blood is collected from healthy newborn babies and frozen. One cord blood collection is called a "cord blood unit." On transplant day, the cord blood will be given through the catheter just like a blood transfusion. Transplants done this way have been successful. However, this type of transplant is fairly new. Therefore, it is important to study it so the doctors can better understand how it works.

Most blood or bone marrow transplants using donor stem cells are done as part of a study. When patients are on a study we test new ways of treating them which we think may be better than the old ways. We collect information about the result of this treatment so we can understand how well the treatment works. This is so we can learn better ways to treat our patients.

There are three chemotherapy drugs involved. They are called fludarabine (5 doses), cyclophosphamide (1 dose), and thiotepa (2 doses). Also two days of radiation therapy. This is called Total Body Irradiation or TBI. The TBI if given for two days before, the transplant. On transplant day, the cord blood cells will be given through a catheter. The immune suppressing drugs given are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through the catheter. Later they can be given as tablets.

Cyclophosphamide 50 mg/kg/dose x 1 IV day -6 (1 dose) Fludarabine 30 mg/m2/dose x 5 IV days -6 to -2 (5 doses) Thiotepa 5 mg/kg/dose x 2 IV days -5 to -4 (2 doses) TBI 200 cGy/dose x 2 days -2 to -1 (2 doses). On transplant day, the cord blood cells will be given through your catheter. The immune suppressing drugs you will receive are called cyclosporine-A (CSA) and mycophenolate mofetil (MMF). These will be started 3 days before the transplant and will be given through your catheter. Later they can be given as tablets.

Eligibility

Ages Eligible for Study:

18 Years to 70 Years

Genders Eligible for Study:

Both

Accepts Healthy Volunteers:

No

Criteria

Inclusion Criteria:

At least one cycle of induction or re-induction chemotherapy or lymphoma chemotherapy or azacitidine or decitabine or tyrosine kinase inhibitor.

Patients aged 18-70 years at initial referral with no available and suitably matched related or unrelated donor.

Acute myelogenous leukemia (AML):

Complete first remission (CR1) at high risk for relapse as defined by:

Known prior diagnosis of myelodysplasia (MDS) or myeloproliferative disorder;

Presence of a high-risk cytogenetic abnormality such as t(9;22), t(1;19), t(4;11) or other MLL rearrangements (11q23)or other high-risk molecular abnormality;

Failure to achieve complete remission after four weeks of induction therapy;

Any patient with newly diagnosed ALL > or = to 50 years-old;

Any patient unable to tolerate consolidation and/or maintenance chemotherapy as would have been deemed appropriate by the treating physician.

Complete second remission (CR2).

Myelodysplastic Syndrome (MDS):

Intermediate-1 International Prognostic Scoring System (IPSS) score with poor risk cytogenetics as defined by IPSS.

Intermediate- 2 or High International Prognostic Scoring System (IPSS) score.

MDS/ myeloproliferative disorder overlap syndromes.

Any score with life threatening cytopenia(s), including red cell or platelet transfusion dependence.

Receipt of at least one cycle of cytotoxic chemotherapy, azacitidine or decitabine.

MDS patients must have < or = to 5% bone marrow myeloblasts and ANC > or = to 0.5 (growth factor supported if necessary) at transplant work-up.

Chronic myelogenous leukemia (CML) patients who have failed or are intolerant of tyrosine kinase inhibitors or patients with other myeloproliferative diseases who are high risk and the intent of therapy is cure.

Any Non-Hodgkins lymphoma (including chronic lymphocytic leukemia) at high-risk of relapse not suitable for either high dose myeloablative conditioning or non-myeloablative conditioning

Eligible patients with DLC NHL will:

have relapsed disease following initial therapy but failed to mobilize or had bone marrow involvement and therefore are not suitable for an autologous transplant OR

have failed an autologous transplant and be in CR after salvage chemotherapy.

Eligible patients with transformed indolent NHL/CLL will:

have CR/PR of the large cell component of their disease after either salvage chemotherapy or an autologous transplant.

Eligible patients with mantle cell NHL will:

be high-risk as such as p53 positivity and be in 1st CR/PR after initial therapy OR have relapsed disease following initial therapy and be in 2nd or 3rd CR/PR after salvage chemotherapy.

Eligible patients with indolent B cell NHL (such as, but not limited to, follicular, small cell or marginal zone NHL) or CLL will have 2nd or subsequent progression (pre-allograft cytoreduction necessary but CR/PR not required).

Timing of UCBT:

Admission for UCBT must be within an acceptable time period after the pre-allograft chemotherapy. This will be defined as within 100 days of the start day of the last cycle of chemotherapy (or decitabine or azacitidine) or other disease active agent).

2 UCB units selected according to current MSKCC unit selection algorithm. High resolution 8 allele HLA typing will be performed. Unit selection will occur based on 8 allele HLA-match and CD34+ dose.

In addition, each unit will have a cryopreserved dose of at least 1.5 x 10^7 total nucleated cells/recipient body weight (TNC/kg).

Units with attached segments for confirmatory typing will be given preference.

Exclusion Criteria:

Diagnosis: acute leukemia in morphologic relapse or with morphologic persistent disease (cytogenetic or molecular persistence/relapse in morphologic CR are eligible); MDS or CML or other myeloproliferative disorder with > 5% blasts.

Prior allogeneic transplant.

Active and uncontrolled infection at time of transplantation.

HIV infection.

Inadequate performance status/ organ function.

Pregnancy or breast feeding.

Patient or guardian unable to give informed consent or unable to comply with the treatment protocol including appropriate supportive care, follow-up and research tests.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00739141